Clinical utility of fMRI in evaluating of LSD effect on pain-related brain networks in healthy subjects.

Objective: We aimed to evaluate the effect of Lysergic acid diethylamide (LSD) on the pain neural network (PNN) in healthy subjects using functional magnetic resonance imaging (fMRI).

Methods: Twenty healthy volunteers participated in a balanced-order crossover study, receiving intravenous administration of LSD and placebo in two fMRI scanning sessions. Brain regions associated with pain processing were analyzed by amplitude of low-frequency fluctuation (ALFF), independent component analysis (ICA), functional connectivity and dynamic casual modeling (DCM).

Results: ALFF analysis demonstrated that LSD effectively relieves pain due to modulation in the neural network associated with pain processing. ICA analysis showed more active voxels in anterior cingulate cortex (ACC), thalamus (THL)-left, THL-right, insula cortex (IC)-right, parietal operculum (PO)-left, PO-right and frontal pole (FP)-right in the placebo session than the LSD session. There were more active voxels in FP-left and IC-left in the LSD session compared to the placebo session. Functional brain connectivity was observed between THL-left and PO-right and between PO-left with FP-left, FP-right and IC-left in the placebo session. In the LSD session, functional connectivity of PO-left with FP-left and FP-right was observed. The effective connectivity between left anterior insula cortex (lAIC)-lAIC, lAIC-dorsolateral prefrontal cortex (dlPFC) and secondary somatosensory cortex (SII)-dlPFC were significantly different. Finally, the correlation between fMRI biomarkers and clinical pain criteria was calculated.

Conclusion: This study enhances our understanding of the LSD effect on the architecture and neural behavior of pain in healthy subjects and provides great promise for future research in the field of cognitive science and pharmacology.